The objectives of this grant application are outlined in two Specific Aims: to identify and characterize antigen-specific T cells both in response to conventional antigens and in lesions of autoimmunity and, secondly, to identify and characterize novel genes expressed in stages of T cell anergy. The first specific aim takes advantage of our recently published observation that cell surface expression of CD4 is markedly increased on antigen-activated T cells and can be used to identify antigen-specific T cells from draining lymph nodes of immunized mice. It has been possible to use this marker to isolate and characterize autoantigen-specific T cells form lesions of autoimmunity (see preliminary data). [By developing GFP transgenic mice on the NOD and B6 backgrounds, we will be able to study the CD4/high T cells in adoptive transfer in modes of autoimmunity.] The second Specific Aim intends to [identify and characterize a set of "anergy associated genes" identified by the technique of differential display (see preliminary data).] By identifying and characterizing such genes and or their products, it may be possible to study mechanisms of anergy induction. Additionally, "anergy-specific" genes will be used as markers to study [T cells in vivo in various models of tolerance or induced unresponsiveness in animal models of immunotherapy and/or transplantation tolerance. Using the GFP transgenic T cells in adoptive transfer will allow isolation and characterization of immunomodulated T cells from the recipient mice.] Utilizing recently developed techniques of retroviral-mediated transduction of murine T cells should allow functional analysis of the new genes described above found in states of T cell anergy.